The administration of proteinic substances has been, from a few years ago, limited to the parenteral route as it was the only one which provided a good absorption to molecules having a complex structure and not able to tolerate environments with a high acidity and rich in proteolytic enzymes such as that ones which can be found in the digestive apparatus. The need to apply the proteinic substances by an invasive parenteral administration, the difficulty in obtaining, on a large scale, many proteins from natural sources, and the very high activity of such substances, with the consequent risks of overdosage, have limited use of such substances in clinical practice.
Recent attempts to orally administer the peptide substances with drug delivery systems such as microparticles and liposomes, did not obtain satisfactory results in absorption or reproduciblity of the same: the transit time variability in the digestive apparatus, associated with, the large presence of proteolytic enzymes, has made the researcher to consider oral administration as a problem.
More recently, in an attempt to avoid the more invasive parenteral administration, formulations suitable for nasal administration of proteinic substances have been proposed.
The typical disadvantage of this way of administration consists in: the relatively reduced area available for the absorption, the high clearance (which reduces the time of contact ) and the particular characteristic of the muconasal epithelium which covers the upper respiratory organs, that is the presence of cilia in association with mucus producing glands.
In addition, the "absorption promoters" frequently used in formulations for nasal administration produce damage to the mucociliary clearance of the deposit zone of the formulation and give problems in regard to repeated or chronic treatment cycles.
With the same aims, rectal administration of protein substances has also been proposed: this administration is nevertheless confined to the mediterranean area and is considered unproposable to the nordamerican and nordeuropean populations. In addition to the ethnical problem, the rectal ampoul has a limited surface and a basic pH.
More recently it has been found that intravaginal administration, till now considered for local treatment only, can be used to allow the systemic absorption of protein substances. The vaginal mucous is in fact able to allow the diffusion of considerable quantities of pharmacologically active substances from the application surface to the dermic stratum which has a rich vascular area able to absorb and drain in the systemic circle, besides the deep dermic stratum.
An important characteristic which allow high absorption values in the vaginal area, as well as for nasal cavity and mucous in general, is the bioadhesion of the formulation.
The formulations commonly used in medical practice take advantage of the vehicle characteristics: its viscosity and composition play an important role on the time of persistence of the drug, and hence effective amount, in the absorption area, as well as the achievement of an opportune absorption area and the extension of the same.
Generally, the lower the mobility of the vehicle, and the higher its viscosity, the more the persistence permanence time increases, and, consequently, the higher the possibility that the active substance is quantitatively absorbed.
Nevertheless, we must not neglect the fact that, usually, a reduced viscosity helps to spread the dispersion of the dosage applied by means of suitable mechanical devices, such as the nasal minipump or foam generators, allowing a very fine distribution of the product. This is very important to increase the contact surface and promote drug absorption.